Paradigm-HF: a Paradigm Shift in Heart Failure Treatment?

The tested concept

Although LCZ696 appears to be the name of a newly invented molecule, it is not exactly that. In fact, it is a mixture of 320 mg of traditional valsartan with sacubitril. Sacubitril is the new drug, which acts by inhibiting neprilysin action. Neprilysin degrades “good” molecules, such as the natriuretic peptide and bradykinin. Therefore, by inhibiting neprilysin, sacubitril increases the concentration of these molecules, which have vasodilating and natriuretic action. Therefore, the burden of proof is on the clinical benefit of sacubitril. Surprisingly, this was not the concept tested in PARADIGM-HF trial.

What has been done in the PARADIGM-HF trial? The standard treatment of the sacubitril group was curiously more appropriate than the standard treatment in the control group. While the sacubitril group patients enjoyed a blockade of the renin-angiotensin-aldosterone system determined by a maximum dose of valsartan (320 mg daily), in the control group patients were given half of the maximum dose of enalapril (20 mg daily, fixed dose).

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